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NM_001273.5(CHD4):c.2506C>T (p.Arg836Cys) AND not provided

Germline classification:
Uncertain significance (2 submissions)
Last evaluated:
Oct 20, 2021
Review status:
2 stars out of maximum of 4 stars
criteria provided, multiple submitters, no conflicts
Somatic classification
of clinical impact:
None
Review status:
(0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided
Somatic classification
of oncogenicity:
None
Review status:
(0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided
Record status:
current
Accession:
RCV001773951.6

Allele description [Variation Report for NM_001273.5(CHD4):c.2506C>T (p.Arg836Cys)]

NM_001273.5(CHD4):c.2506C>T (p.Arg836Cys)

Gene:
CHD4:chromodomain helicase DNA binding protein 4 [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
12p13.31
Genomic location:
Preferred name:
NM_001273.5(CHD4):c.2506C>T (p.Arg836Cys)
HGVS:
  • NC_000012.12:g.6593424G>A
  • NG_052823.1:g.19016C>T
  • NM_001273.5:c.2506C>TMANE SELECT
  • NM_001297553.2:c.2485C>T
  • NM_001363606.2:c.2467C>T
  • NP_001264.2:p.Arg836Cys
  • NP_001284482.1:p.Arg829Cys
  • NP_001350535.1:p.Arg823Cys
  • NC_000012.11:g.6702590G>A
  • NM_001273.2:c.2506C>T
Protein change:
R823C
Links:
dbSNP: rs933562750
NCBI 1000 Genomes Browser:
rs933562750
Molecular consequence:
  • NM_001273.5:c.2506C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001297553.2:c.2485C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001363606.2:c.2467C>T - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Synonyms:
none provided
Identifiers:
MedGen: C3661900

Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV001994401GeneDx
criteria provided, single submitter

(GeneDx Variant Classification Process June 2021)		Uncertain significance
(Aug 18, 2019) 		germlineclinical testing

Citation Link,

SCV002289748Labcorp Genetics (formerly Invitae), Labcorp
criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))		Uncertain significance
(Oct 20, 2021) 		germlineclinical testing

PubMed (1)
[See all records that cite this PMID]

Help

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineyesnot providednot providednot providednot providednot providedclinical testing
not providedgermlineunknownnot providednot providednot providednot providednot providedclinical testing

Citations

PubMed

Sherloc: a comprehensive refinement of the ACMG-AMP variant classification criteria.

Nykamp K, Anderson M, Powers M, Garcia J, Herrera B, Ho YY, Kobayashi Y, Patil N, Thusberg J, Westbrook M; Invitae Clinical Genomics Group., Topper S.

Genet Med. 2017 Oct;19(10):1105-1117. doi: 10.1038/gim.2017.37. Epub 2017 May 11. Erratum in: Genet Med. 2020 Jan;22(1):240. doi: 10.1038/s41436-019-0624-9.

PubMed [citation]
PMID:
28492532
PMCID:
PMC5632818

Details of each submission

From GeneDx, SCV001994401.2

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testingnot provided

Description

Not observed in large population cohorts (Lek et al., 2016); In silico analysis, which includes protein predictors and evolutionary conservation, supports a deleterious effect; Has not been previously published as pathogenic or benign to our knowledge

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineyesnot providednot providednot providednot providednot providednot providednot provided

From Labcorp Genetics (formerly Invitae), Labcorp, SCV002289748.3

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (1)

Description

In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Benign"; Align-GVGD: "Class C55"). This variant has not been reported in the literature in individuals affected with CHD4-related conditions. This variant is not present in population databases (ExAC no frequency). This sequence change replaces arginine with cysteine at codon 836 of the CHD4 protein (p.Arg836Cys). The arginine residue is moderately conserved and there is a large physicochemical difference between arginine and cysteine.

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineunknownnot providednot providednot providednot providednot providednot providednot provided

Last Updated: Sep 29, 2024